Therapeutic radiopharmaceuticals generally incorporate a strong beta or alpha emitting radionuclide. Severe chemical damage may be caused by such radionuclides if the radionuclides are not handled properly. Radioactive pharmaceuticals, however, are widely used for diagnosis and treatment of certain illnesses such as cancer and heart disease. For diagnostic purposes, radioactive complexes have been used to provide both negative and positive images of body organs, skeletal images and the like.
For most applications of radiopharmaceuticals, the nonradioactive portion of the complex to be used is prepared and stored until time for administration to the patient, at which time the radioactive portion of the complex is added to form the radiopharmaceutical of interest. Examples of this are disclosed in U.S. Pat. Nos. 3,984,227 (1976) and 4,652,440 (1987). Further, in many situations, the radioactive component of the complex must be generated and/or purified at the time the radiopharmaceutical is prepared for administration to the patient. U.S. Pat. No. 4,778,672, assigned to the University of Cincinnati, (1988) describes, for example, a method for purifying pertechnetate and perrhenate for later use in a radiopharmaceutical. EP 250966, also assigned to the University of California (1988) describes a method for obtaining a sterile, purified complexed radioactive perrhenate from a mixture which includes, in addition to the ligand-complexed radioactive perrhenate, uncomplexed ligand, unligated perrhenate, rhenium dioxide and various other compounds. Specifically, the application teaches a method for purifying a complex of rhenium-186 and 1-hydroxyethylidene diphosphonate (HEDP) from a crude solution. In the process of forming the complex, high quantities of reductant are required for the reduction of perrhenate to achieve chelation. This process results in excess ligand and reductant in the crude solution. Partially because of the necessity of removing excess ligand and reductant to avoid high uptake of the radioactive complexes in soft tissue, further purification of the rhenium complex (the rhenium is in the form of radioactive ligand-complexed perrhenate) by a low pressure or gravity flow chromatographic procedure is required. Another reason for purification by anion exchange chromatography of the crude rhenium solution is to remove the unstable species and obtain the more thermodynamically stable product. This purification involves the aseptic collection of several fractions which elute from the separation medium used in the particular chromatographic procedure, followed by a determination of exactly which fractions to combine. After combining the selected fractions, the fractions are sterile filtered and diluted prior to injection into the patient. The purified rhenium complex must be injected into the patient within one hour of preparation to avoid the possibility of degradation. Thus, a rhenium complex may have to be purified twice before use, causing inconvenience and possible dangers to the user.
There is a need in the art for a method of preparing a stabilized radio-pharmaceutical ready for use in diagnostic or therapeutic applications. Further, there is a need in the art for a method of preparing rhenium therapeutic agents that do not need to undergo a purification step prior to use.